This study has been set up within the framework of the INNODIA network. INNODIA is a global partnership between 31 academic institutions, 6 industrial partners, a small sized enterprise and 2 patient organizations, bringing their knowledge and experience together with one common goal: "To fight type 1 diabetes". (www.innodia.eu) The overall aim of INNODIA is to advance in a decisive way how to predict, stage, evaluate and prevent the onset and progression of type 1 diabetes (T1D). For this, INNODIA has established a comprehensive and interdisciplinary network of clinical and basic scientists, who are leading experts in the field of T1D research in Europe and UK (United Kingdom), with complementary expertise from the areas of immunology, Beta-cell biology, biomarker research and T1D therapy, joining forces in a coordinated fashion with industry partners and two foundations, as well as with all major stakeholders in the process, including regulatory bodies and patients with T1D and their families.
The study is a multicenter, randomized, double-blind, placebo-controlled study in volunteers with newly diagnosed diabetes mellitus type 1 (within 6 weeks after diagnosis). The purpose of the clinical trial is to confirm the effect of 360mg Verapamil sustained release (SR) administered orally once daily (titrated over the first 3 months from 120 mg to 360 mg) on the preservation of beta-cell function measured as stimulated C-peptide after 12 months compared to placebo. The study has a cross-over design and a duration of approximately 24 months, consisting of 3 telephone visits and 7 visits at the trial site. The duration of the treatment phase with verapamil is 12 months, and an additional (optional) follow-up visit will be carried out 12 months after completion of the study. The study procedures are identical in all 20 clinical centres across Europe and the UK.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
136
For use as a test product in this blinded study, the IMP will be modified by re-packaging. The film-coated tablets will be squeezed from their blisters and filled into HDPE Twist-Off bottles. Each bottle will be labeled as required per country requirement. Labels will be blinded. Drug administration: * from Day 0 to Week 4: 120 mg once daily * from Week 4 to Week 8: 240 mg once daily * from Week 8 to Month 12: 360 mg once daily
The matching placebo will be filled into HDPE Twist-Off bottles, in the same way as the verum. Each bottle will be labeled as required per country requirement. Labels will be blinded. Drug administration: * from Day 0 to Week 4: 120 mg once daily * from Week 4 to Week 8: 240 mg once daily * from Week 8 to Month 12: 360 mg once daily
Medical University of Graz, Department of Internal Medicine Division of Endocrinology and Metabolism
Graz, Styria, Austria
Universitair Ziekenhuis Brussel
Brussels, Belgium
Université Libre de Bruxelles/ Hôpital Erasme
Brussels, Belgium
Universitair Ziekenhuis Antwerpen
Edegem, Belgium
Katholieke Universiteit Leuven
Leuven, Belgium
Institut National de la Santé et de la Recherche Médicale
Paris, France
HKA Hannover
Hanover, Germany
Universität Ulm
Ulm, Germany
Università Vita-Salute San Raffaele
Milan, Italy
Università degli Studi di Siena
Siena, Italy
...and 12 more locations
Area under the stimulated C-peptide response curve
The primary objective is to determine the changes in stimulated C-peptide response during the first two hours of a mixed meal tolerance test (MMTT) at baseline and after 12 months for 360mg Verapamil SR administered orally once daily versus placebo.
Time frame: At 12 months
Area under the stimulated C-peptide response curve
The area under the stimulated C-peptide response curve over the first two hours of a mixed meal tolerance test (MMTT)
Time frame: At 3, 6, 9 and 24 months
Proinsulin, Insulin, Pro-IAPP and Proglucagon secretion
Proinsulin, Insulin, Pro-IAPP and Proglucagon secretion during the first two hours of a mixed meal tolerance test (MMTT)
Time frame: At baseline and 3, 6, 9 and 12 months
Fasting C-peptide
To determine the effects of 360mg Verapamil SR administered orally once daily on fasting C-peptide and Dried Blood Spot (DBS) C-peptide measurements over time.
Time frame: At 12 months
DBS C-peptide
The DBS (Dried blood spot) C-peptide measurements at all observation times
Time frame: At baseline, week 4, week 8, and 3, 6, and 9 months
Change in HbA1c
To determine the effects of 360mg Verapamil SR administered orally once daily on HbA1c daily total insulin dose and continous glucose monitoring (CGM) time in range.
Time frame: Baseline, 12 and 24 months
Severe hypoglycaemic episodes
Number of treatment emergent severe hypoglycaemic episodes. Severe hypoglycaemia denotes severe cognitive impairment requiring external assistance for recovery according to the American Diabetes Association (ADA)
Time frame: Baseline to 12 months
DKA
Number of treatment emergent episodes of diabetic ketoacidosis
Time frame: Baseline to 12 months
Change in insulin requirements
Change in insulin requirements, baseline to 12 months as the daily total dose (three days average) in units per kg body weight (BW)
Time frame: Baseline, 12 and 24 months
Change in T1D associated autoantibodies
Change in T1D associated autoantibodies (GADA, IAA, IA-2A and ZnT8A) from baseline to 12 months
Time frame: Baseline to 12 months
Continous glucose monitoring (CGM)
Continous glucose monitoring (CGM) time in range (70-140 mg/dL, 3.9-7.8 mmol/L) and (70-180 mg/dL, 3.9-10.0 mmol/L), time above range (\>180 mg/dL, \>10.0 mmol/L), time below range (\<70 mg/dL, \< 3.9 mmol/L)
Time frame: At Baseline and every 2 weeks prior to each visit (week 4, week 8, and 3, 6, and 9 months)
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